2.Progress in genetic and epigenetic research on in-stent restenosis after percutaneous coronary interventions.
Yan-hong KANG ; Hai-yan LAO ; Xi-yong YU ; Ji-yan CHEN ; Shi-long ZHONG
Chinese Journal of Medical Genetics 2012;29(1):38-42
Coronary heart disease is one of the most important causes of death in human, and consumes vast medical resources. Percutaneous coronary intervention (PCI) has been a significant breakthrough for its treatment. However, clinical application has been hampered by in-stent restenosis (ISR). Although drug eluting stent (DES) has reduced the occurrence of restenosis, incidence of ISR is still about 5% to 10%. The main reasons for restenosis after PCI are hyperplasia of vascular endothelial cells and smooth muscle cell migration. The exact mechanism of personalized differences in restenosis is not clear yet, but there may be a variety of risk factors. In addition to aging, smoking and diabetes, an increasing number of studies have found that genetic and epigenetic factors play an important role in ISR. In this article, authors have reviewed genetic and epigenetic factors on the progression of ISR, which may help to determine the genetic risk factors in patients with ISR after PCI.
Angioplasty, Balloon, Coronary
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methods
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Coronary Restenosis
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etiology
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genetics
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Disease Progression
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Epigenomics
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methods
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Humans
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Stents
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Treatment Outcome
3.Analysis on allele frequencies of 7 short tandem repeat loci of Kashing-Beck disease patients on.
Long-li KANG ; Xiong GUO ; Hong ZUO ; Zhi-guang PING ; Bao-di ZHANG ; Jianghua LAI ; Dong GENG
Chinese Journal of Epidemiology 2005;26(10):790-793
OBJECTIVETo analyze the allele frequencies of 7 short tandem repeat (STR) loci (D12S1718, D12S1675, D12S358, D12S367, D12S1638, D12S1646 and D12S1682) on chromosome 12 among Kashing-Beck disease (KBD) patients and the control population living in the KBD areas and non-KBD area.
METHODSEDTA-blood specimens were collected from 102 unrelated individuals of Chinese Han population in Shaanxi province including 29 KBD patients,30 controls living in the KBD area and 43 living in the non-KBD area. DNA samples were extracted using the Wizard Genomic DNA purification kit (http://www. Promega. com) and were amplified by polymerase chain reaction (PCR) technique. The PCR products were analyzed by ABI 3100 Genetic Analyzer.
RESULTS(1) In KBD patients group, the allele number for 7 STR loci were 4,7,7,8,5,5 and 7, the genotype number were 5,12,13,11,10,9 and 13; (2) In the control population living in KBD area, the allele number for 7 STR loci were 4,9,7,6,6,6 and 8,t he genotype number were 5,10,12,14,12,9 and 13;(3) In the control population living in the non-KBD area, the allele number for 7 STR loci were 7,9,7,7,5,8 and 11, the genotype number were 9,16, 17,16,12,15 and 20;(4) Compared with the allele frequencies among three groups, there were significant differences between KBD patients and the controls living in the KBD area (D12S367: P = 0.034; D12S1638: P = 0.041) and the controls living in the non-KBD area (D12S367: P = 0. 029; D12S1638: P= 0 .028) in the D12S367 and D12S1638 loci; (5) There were significant differences among KBD patients (P = 0.036), controls living in the KBD area (P = 0.039) and controls living in the non-KBD area in the D12S1646.
CONCLUSIONThere was significant difference between KBD patients and the controls in the D12S367 and D12S1638 loci.
Adult ; Case-Control Studies ; Child ; Chromosomes, Human, Pair 12 ; genetics ; Female ; Gene Frequency ; Genetic Loci ; genetics ; Genotype ; Humans ; Joint Diseases ; genetics ; Male ; Microsatellite Repeats ; genetics
4.Comparison of Hsps expression after radio-frequency field exposure in three human glioma cell lines.
Gui-Rong DING ; Xiao-Wu WANG ; Kang-Chu LI ; Lian-Bo QIU ; Sheng-Long XU ; Juan TAN ; Guo-Zhen GUO
Biomedical and Environmental Sciences 2009;22(5):374-380
OBJECTIVETo investigate and compare the effect of radio-frequency (RF) field exposure on expression of heat shock proteins (Hsps) in three human glioma cell lines (MO54, A172, and T98).
METHODSCells were exposed to sham or 1950 MHz continuous-wave for 1 h. Specific absorption rates (SARs) were 1 and 10 W/kg. Localization and expression of Hsp27 and phosphorylated Hsp27 ((78) Ser) (p-Hsp27) were examined by immunocytochemistry. Expression levels of Hsp27, p-Hs27, and Hsp70 were determined by Western blotting.
RESULTSThe Hsp27 was primarily located within the cytoplasm, p-Hsp27 in both cytoplasm and nuclei of MO54, A172, and T98 cells. RF field exposure did not affect the distribution or expression of Hsp27. In addition, Western blotting showed no significant differences in protein expression of Hsp27 or Hsp70 between sham- and RF field-exposed cells at a SAR of 1 W/kg and 10 W/kg for 1 h in three cells lines. Exposure to RF field at a SAR of 10 W/kg for 1 h slightly decreased the protein level of phosphorylated Hsp27 in MO54 cells.
CONCLUSIONThe 1950 MHz RF field has only little or no apparent effect on Hsp70 and Hsp27 expression in MO54, A172, and T98 cells.
Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; radiation effects ; Glioma ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Neoplasm Proteins ; genetics ; metabolism ; Neuroglia ; radiation effects ; Protein Transport
5.Genetic and epigenetic predispositions underlying cardiovascular outcomes among patients treated with clopidogrel and aspirin
Wan-Ping ZHONG ; He-Ping LEI ; Hong WU ; Ji-Yan CHEN ; Xi-Yong YU ; Yan-Hong KANG ; Li-Yun CAI ; Meng-Zhen ZHANG ; Li-Ping MAI ; Shi-Long ZHONG
Chinese Journal of Pharmacology and Toxicology 2018;32(4):343-344
Coronary artery disease (CAD)is a major cause of death and disability worldwide, and consumes a considerable amount of medical resources every year.Clopidogrel is a first-line antiplate-let therapy for CHD, butit is associated with substantial variability in PK and pharmacodynamics re-sponse. To date, gene variants explain only a smallproportion of the variability.The study aimed to identify new genetic loci-modifying antiplatelet response to clopidogrel in Chinese patients with CAD by a systematic analysis combining antiplatelet effects and PK, and further to investigate the PON1 gene promoter DNA methylation and genetic variations possibly influencing clinical outcomes in pa-tients undergoing PCI. We identified novel variants in two transporter genes (SLC14A2rs12456693, ATP-binding cassette [ABC]A1 rs2487032) and in N6AMT1 (rs2254638) associated with P2Y12 reac-tion unit (PRU) and plasma active metabolite (H4) concentration. These new variants dramatically im-proved the predictability of PRU variability to 37.7%. The associations between these loci and PK pa-rameters of clopidogrel and H4 were observed in additional patients, and its function on the activation of clopidogrel was validated in liver S9 fractions (P<0.05). Rs2254638 was further identified to exert a marginal risk effect formajor adverse cardiac events in an independent cohort.Multivariate logistic regression analysis indicated that PON1methylation level at CpG site-161 (OR=0.95; 95% CI=0.92–0.98;P<0.01)and the use of angiotensin converting enzyme inhibitors(OR=0.48;95% CI=0.26–0.89;P<0.01) were associated with decreased risk of bleeding events. In conclusion, new genetic variants were systematically identified as risk factors for the reduced efficacy of clopidogrel treatment.The ab-normal expression of DNA methylation-regulating key genes in the pharmacokinetic and pharmacody-namics pathways of clopidogrel and aspirin may modify clinical outcomes in dual antiplatelet-treated pa-tients undergoing PCI.
6.Predictive value of new type critical illness score scale for patients transferred to intensive care units and death
Yuanchen XI ; Jing KANG ; Yamei LIU ; Long TIAN ; Chenyu WANG
Chongqing Medicine 2024;53(14):2138-2142
Objective To create the new type critical illness score scale based on logistic regression pre-diction model,and to evaluate its predictive value for the patient transferring to intensive care unit (ICU) and death.Methods The clinical data in 1000 patients were retrospectively collected from the HIS system of this hospital from October 2022 to October 2023.The new critical illness score scale was created based on the model in predicting the ICU transfer rate created by the previous studies.The modified early warning score (MEWS) and acute physiology and chronic health evaluation Ⅱ (APCHEⅡ) score served as reference respec-tively,the predictive value of the new type critical illness score scale for patient transferring to ICU and death was evaluated by using the receiver operating characteristic (ROC) curve and area under curve (AUC).Results The ICU transfer rate of the patients was 29.8%,and the mortality rate was 8.10%.The new type critical illness score scale,MEWS and APCHEⅡ scores of the patients who were transferred to ICU or died were significant-ly higher than those of the patients who were not transferred to ICU or died (P<0.05).The predictive value of the new critical illness scale,MEWS,and APCHEⅡ scores for ICU transfer was high (P<0.05).AUC was 0.917,0.922 and 0.934 respectively,the sensitivity was 82.26%,84.22% and 90.57% respectively,the speci-ficity was 80.36%,73.50% and 83.45% respectively and the Youden index was 62.62%,57.72% and 74.02%,respectively.The predictive value of the new type critical illness score scale,MEWS and APCHEⅡ scores for the death was high (P<0.05).AUC was 0.924,0.914 and 0.933 respectively,the sensitivity was 93.48%,86.38% and 84.67% respectively,the specificity was 73.46%,79.38% and 88.69% respectively,and the Youden index was 66.94%,65.76% and 73.36% respectively.Conclusion The predictive value of the new type critical illness score scale for the patients transferring to ICU and death is basically consistent with that of the traditional scales,which could serve as a new evaluation tool for ICU patients.
7.Mechanisms of resistance to ceftazidime/avibactam of carbapenem-resis-tant Klebsiella pneumoniae
Xi-Yuan CHEN ; Zi-Ling WANG ; Shuang SONG ; Bo-Yin XU ; Jing-Fang SUN ; Shu-Long ZHAO ; Hai-Quan KANG
Chinese Journal of Infection Control 2024;23(11):1365-1372
Objective To explore the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP),and reveal its mechanism of resistance to ceftazidime/avibactam(CZA).Methods CZA-re-sistant CRKP strains initially isolated from the Affiliated Hospital of Xuzhou Medical University from January 2021 to September 2023 were collected.The carriage of 5 carbapenemase genes(blaKPC,blaNDM,blaOXA,blaVIM,blaIMp)were detected with gene amplification method and colloidal gold method.The relative copy number and expression level of Klebsiella pneumoniae(KP)carbapenemase-producing KP(KPC-KP)was detected with real-time quantita-tive polymerase chain reaction(RT-qPCR),mutation sites of KPC mutation strains were analyzed with whole-ge-nome sequencing,and epidemic characteristics of CRKP and resistance mechanism to CZA were analyzed.Results A total of 73 CZA-resistant CRKP strains were isolated,with 37(50.68%)being KPC and NDM co-producing strains,33(45.21%)NDM-producing alone(23 strains producing NDM-5 and 10 strains producing NDM-1),and 3 KPC-producing alone.KP-2842 strain was identified as ST11-type KPC-33 variant,KP-2127 and KP-2189 strains produced KPC-2.Compared with KP ATCC BAA-1705,the copy number of blaKPC in these strains up-regulated by 1.04-3.86 fold,and the expression increased by 6.66-12.93 fold,respectively.Colloidal gold and PCR methods demonstrated good consistency and the ability to detect the enzyme co-producing and KPC-33 variant.Conclusion In this hospital,the resistance of CRKP to CZA is primarily mediated by the metalloenzyme NDM,with co-produc-tion of NDM and KPC being a characteristic of CRKP.High copy number and expression level of blaKPC-2 also con-tribute to CZA resistance.This study identified the KPC-33 variant for the first time in ST11-type CRKP in Jiangsu Province.
8.Genome Assembly of Alfalfa Cultivar Zhongmu-4 and Identification of SNPs Associated with Agronomic Traits
Long RUICAI ; Zhang FAN ; Zhang ZHIWU ; Li MINGNA ; Chen LIN ; Wang XUE ; Liu WENWEN ; Zhang TIEJUN ; Yu LONG-XI ; He FEI ; Jiang XUEQIAN ; Yang XIJIANG ; Yang CHANGFU ; Wang ZHEN ; Kang JUNMEI ; Yang QINGCHUAN
Genomics, Proteomics & Bioinformatics 2022;20(1):14-28
Alfalfa(Medicago sativa L.)is the most important legume forage crop worldwide with high nutritional value and yield.For a long time,the breeding of alfalfa was hampered by lacking reliable information on the autotetraploid genome and molecular markers linked to important agro-nomic traits.We herein reported the de novo assembly of the allele-aware chromosome-level genome of Zhongmu-4,a cultivar widely cultivated in China,and a comprehensive database of genomic variations based on resequencing of 220 germplasms.Approximate 2.74 Gb contigs(N50 of 2.06 Mb),accounting for 88.39%of the estimated genome,were assembled,and 2.56 Gb contigs were anchored to 32 pseudo-chromosomes.A total of 34,922 allelic genes were identified from the allele-aware genome.We observed the expansion of gene families,especially those related to the nitrogen metabolism,and the increase of repetitive elements including transposable elements,which probably resulted in the increase of Zhongmu-4 genome compared with Medicago truncatula.Population structure analysis revealed that the accessions from Asia and South America had rela-tively lower genetic diversity than those from Europe,suggesting that geography may influence alfalfa genetic divergence during local adaption.Genome-wide association studies identified 101 sin-gle nucleotide polymorphisms(SNPs)associated with 27 agronomic traits.Two candidate genes were predicted to be correlated with fall dormancy and salt response.We believe that the allele-aware chromosome-level genome sequence of Zhongmu-4 combined with the resequencing data of the diverse alfalfa germplasms will facilitate genetic research and genomics-assisted breeding in variety improvement of alfalfa.
9.Transmission disequilibrium test for 15 short tandem repeat loci in Kashin-Beck disease and their interaction with low selenium.
Xiao-Wei SHI ; Ai-Li LV ; Feng-Ling REN ; Wen-Rong LI ; Long-Li KANG ; Xiong GUO
Journal of Southern Medical University 2011;31(4):567-571
OBJECTIVETo identify the genetic susceptibility to Kashin-Beck disease (KBD) and explore the interaction between low selenium (Se) and the susceptibility gene loci in KBD.
METHODSThe DNA samples collected from 23 KBD nuclear families were analyzed using PCR and GeneScan Analysis 3.7 and Genotyper3.7 software. The haplotype relative risk (HRR) and transmission disequilibrium test (TDT) were used to test the data of the genotypes. The serum selenium (Se) concentration was measured by atomic fluorescence spectrometry, and the interaction between low Se and the susceptibility loci was calculated using a binary logistic regression.
RESULTSIn the 23 nuclear families, the alleles of D2S151 (248 bp), D2S305 (320 bp), and D11S4094 (194 bp) showed significant correlation to KBD (P<0.05). Serum Se concentrations in the studied individuals was 0.037 µg/ml. No significant statistical interaction was observed between low Se exposure and the susceptibility loci (P>0.05).
CONCLUSIONThe polymorphisms in the STR loci D2S305, D2S151, and D11S4094 or the polymorphism loci near them might been related to KBD susceptibility. Low Se exposure shows no significant interaction with the susceptibility loci.
Adolescent ; Adult ; Alleles ; Child ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Kashin-Beck Disease ; blood ; etiology ; genetics ; Male ; Microsatellite Repeats ; Middle Aged ; Pedigree ; Selenium ; blood ; Young Adult
10.Outcome of catheter ablation of atrial fibrillation in patients with prior ischemic stroke.
Song-Nan LI ; Jun-Ping KANG ; Xin DU ; Xiao-Nan HE ; De-Yong LONG ; Rong-Hui YU ; Ri-Bo TANG ; Cai-Hua SANG ; Chen-Xi JIANG ; Man NING ; Jian-Zeng DONG ; Chang-Sheng MA
Chinese Medical Journal 2013;126(6):1033-1038
BACKGROUNDCatheter ablation for atrial fibrillation (AF) has been demonstrated to be effective in a subsets of patients with AF. However, very few data are available in regard to patients with prior history of stroke undergoing catheter ablation. This study aimed to investigate the outcome of catheter ablation in AF patients with prior ischemic stroke.
METHODSBetween January 2008 and December 2011, of 1897 consecutive patients who presented at Beijing An Zhen Hospital for treatment of drug-refractory AF, 172 (9.1%) patients in the study population had a history of ischemic stroke. All patients underwent catheter ablation and were followed up to assess maintenance of sinus rhythm and recurrence of symptomatic stroke.
RESULTSAmong these 1897 patients, 1768 (93.2%) who had complete follow-up information for a minimum of six months were included in the final analysis. Patients in the stroke group (group I) and the no-stroke group (group II) were similar in regards to gender, body mass index (BMI), history of diabetes, type of AF, and left atrial size. The patients in group I were older than those in group II, and had a higher incidence of hypertension, chronic heart failure, lower left ventricular ejection fraction (LVEF), and higher CHADS2 scores. Six months after ablation, 107 (68.6%) patients in group I and 1403 (87.1%) in group II had discontinued warfarin treatment (P < 0.001). During a median follow-up of (633 ± 415) days, 65 patients in the group I and 638 in group II experienced AF recurrence, and five patients in group I and 28 in group II developed symptomatic stroke. The rates of AF recurrence and recurrent stroke were similar between group I and group II (41.7% vs. 39.6%, P = 0.611; 3.2% vs. 1.7%, P = 0.219; respectively).
CONCLUSIONCatheter ablation of AF in patients with prior stroke is feasible and efficient.
Aged ; Atrial Fibrillation ; surgery ; Catheter Ablation ; methods ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stroke ; surgery